Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis

Christina S. Hirsch, Zahra Toossi, Guido Vanham, John L. Johnson, Pierre Peters, Alphonse Okwera, Roy Mugerwa, Peter Mugyenyi, Jerrold J. Ellner

Research output: Contribution to journalArticle

Abstract

Mycobacterium tuberculosis (MTB)-induced T cell responses are depressed in peripheral blood mononuclear cells of persons with newly diagnosed pulmonary tuberculosis (TB), and levels of interferon (IFN)-γ remain low even after completion of antituberculous therapy. Loss of MTB-reactive T cells through apoptotic mechanisms could account for this prolonged T cell hyporesponsiveness. T cell apoptosis was studied in TB patients and healthy control subjects. Both spontaneous and MTB-induced apoptosis (in CD4 and non- CD4 T cells) from TB patients was increased when compared with healthy control subjects, whereas coculture with control antigen (candida) had no effect on T cell apoptosis in either group of study subjects. An inverse correlation existed between increased MTB-induced T cell apoptosis and IFN- γ and interleukin (IL)-2 immunoreactivities. Successful antituberculous chemotherapy resulted in a 50% reduction in both spontaneous and MTB-induced apoptosis, which coincided with 3- and 8-fold increases in levels of MTB- stimulated IL-2 and IFN-γ, respectively. These data indicate that apoptotic pathways are operant during active MTB infection and may contribute to deletion of MTB-reactive T cells and the immunopathogenesis of this disease.

Original languageEnglish (US)
Pages (from-to)945-953
Number of pages9
JournalJournal of Infectious Diseases
Volume179
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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  • Cite this

    Hirsch, C. S., Toossi, Z., Vanham, G., Johnson, J. L., Peters, P., Okwera, A., Mugerwa, R., Mugyenyi, P., & Ellner, J. J. (1999). Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis. Journal of Infectious Diseases, 179(4), 945-953. https://doi.org/10.1086/314667